CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.

Conference Paper

The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here we present evidence that acetylation controlled by Coenzyme A synthase (COASY) and acetyltransferase CBP constitutes a novel mechanism that ensures faithful mitosis. We found that COASY knockdown triggers prolonged mitosis and multinucleation. Acetylome analysis reveals that COASY inactivation leads to hyper-acetylation of proteins associated with mitosis, including CBP and an Aurora A kinase activator, TPX2. During early mitosis, a transient CBP-mediated TPX2 acetylation is associated with TPX2 accumulation and Aurora A activation. The recruitment of COASY inhibits CBP-mediated TPX2 acetylation, promoting TPX2 degradation for mitotic exit. Consistently, we detected a stage-specific COASY-CBP-TPX2 association during mitosis. Remarkably, pharmacological and genetic inactivation of CBP effectively rescued the mitotic defects caused by COASY knockdown. Together, our findings uncover a novel mitotic regulation wherein COASY and CBP coordinate an acetylation network to enforce productive mitosis.

Full Text

Duke Authors

Cited Authors

  • Lin, C-C; Kitagawa, M; Tang, X; Hou, M-H; Wu, J; Qu, DC; Srinivas, V; Liu, X; Thompson, JW; Mathey-Prevot, B; Yao, T-P; Lee, SH; Chi, J-T

Published Date

  • March 12, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 1039 -

PubMed ID

  • 29531224

Pubmed Central ID

  • PMC5847545

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-03422-6

Conference Location

  • England